Castillo earned a scholarship worth $500 to attend Texas A&I after spending a semester at Monterrey Tech. He played college football while enrolled.
Castillo played for the San Antonio Gunslingers of the USFL from 1984–1985, mainly on special teams. In 1984, Castillo saw action in six games, making four tackles and three assists. In 1985, Castillo played in seven games, making eight tackles and registering three assists on a 5–13 club.
Castillo coached linebackers and was the defense line coach at Kingsville High School from 1986–1989.
Castillo was the defensive line coach for Texas A&M University–Kingsville from 1982–1985 and from 1990–1994 he was the offensive line coach. Four offensive linemen he coached ended up in the NFL: Jermane Mayberry, Jorge Diaz, Kevin Dogins, and Earl Dotson.
The Philadelphia Eagles hired Castillo as an offensive assistant in 1995 under Ray Rhodes. In 1996, the Eagles drafted Jermane Mayberry, an offensive lineman Castillo coached at Texas A&M University–Kingsville, in the first round of the 1996 NFL Draft. Castillo was promoted to tight ends coach in 1997, and switched to coaching the offensive line in 1998. When Andy Reid was hired as the head coach of the Eagles in 1999, he retained Castillo on the coaching staff. Mayberry earned a Pro Bowl berth in 2002, and said Castillo "molded me into the player I became." Castillo coached the offensive line for thirteen seasons, from 1998–2010.
Castillo became the defensive coordinator for the Eagles following the firing of Sean McDermott on February 2, 2011. The hiring was met with surprise by players, fans, and members of the media primarily because Castillo had not coached the defensive side of the ball since he was at Kingsville in 1989.
After a tumultuous tenure, Juan Castillo was fired on October 16, 2012. He was replaced by Todd Bowles, the team's secondary coach and former interim head coach of the Miami Dolphins.
Juan was the offensive line coach for the Baltimore Ravens. Added to the Ravens' coaching staff on January 21, 2013, he earned a Super Bowl ring in Super Bowl XLVII, when the Ravens defeated the San Francisco 49ers.
Castillo is married; he and his wife, Zaida, have four sons: Gregory, John, Andres and Antonio. Gregory (born 1990) is currently a cornerback at the University of Iowa. John is currently a distance runner at Villanova University, while Andres is a junior Quarterback at Our Lady of Good Counsel in Olney, MD.
On August 17, 1998, Castillo fractured his left tibial plateau after he was hit by a utility truck outside of Veterans Stadium. Even though he was on crutches, he still coached practice the following day.
In 2002, Castillo and his wife were invited to a Cinco de Mayo celebration by President George W. Bush at the White House.
Port Isabel, Texas declared July 4, 2009 to be "Juan Castillo Day" and presented Castillo with a key to the city.